In the developing world cervical cancer is the third most common cancer in women and the leading cause of cancer death (www.nccc-online.org/) and is particularly insidious in that the majority of cases are among women of childbearing age. The lack of infrastructure in these countries makes the need for a see and treat methodology acute and the only rational approach to the management of the disease. In the developed world this approach also has significant cost benefit possibilities. Techniques based on quantitative optical spectroscopy have been shown in pilot studies to meet this need. Rigorous technology assessment is needed to introduce a new technology clinically. This requires that emerging devices move from pilot study to larger screening and diagnostic trials and on to randomized clinical trials. In this program project we are conducting, to our knowledge, the largest trials of optical spectroscopy with statistically justified sample sizes and consensus-read biopsies as the gold standard. These trials are ahead of schedule and are half way to completion. Completion of these multi center trials is critical for these technologies to advance. We plan to complete these trials so that we have validated the algorithms to be used in the randomized clinical trial of project 3. Additionally in project 2 we will pilot test two new devices which are capable of imaging the entire cervix. Using the same model of technology assessment, we will advance this imaging technology from pilot studies to large diagnostic and screening trials. The specific alms of this proposal are to carry out a series of six clinical trials designed to rigorously evaluate the sensitivity and specificity of fluorescence and reflectance spectroscopy and quantitative cyto-histopathology, as well as to explore the sensitivity and specificity which can be achieved using multispectral optical imaging as a single procedure or in conjunction with optical spectroscopy. Preliminary analyses of the data have revealed sever/d critical findings. First, emission spectra from only two excitation wavelengths are required to achieve optimal diagnostic performance, and that sensitivity and specificity do not significantly increase as excitation wavelengths are added. This preliminary analysis yielded the excitation wavelengths needed to design the MDC. Second, reflectance spectroscopy also contains significant diagnostic information, and that the combination of fluorescence and reflectance spectroscopy provides the best discriminatory capability. We particularly encouraged by the high sensitivity (94%) and specificity (80%) for discrimination of squamous normal and high grade SIL, which exceeds that found in our previous trials. Third, while there are small changes in spectra that occur throughout the cycle, these changes do not achieve statistical significance for the excitation wavelengths used in the diagnostic algorithms. These algorithms perform equally well when applied to data collected throughout the cycle.